Petrich Thorsten, Quintanilla-Martinez Leticia, Korkmaz Zekiye, Samson Elenore, Helmeke Hans Jürgen, Meyer Geerd Jürgen, Knapp Wolfram H, Pötter Eyck
Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Hanover, Germany.
Clin Cancer Res. 2006 Feb 15;12(4):1342-8. doi: 10.1158/1078-0432.CCR-05-1576.
The sodium/iodide symporter (NIS) gene is currently explored in several trials to eradicate experimental cancer with radiodine ((131)I) by its beta-emission. We recently characterized NIS-specific cellular uptake of an alternative halide, radioastatine ((211)At), which emits high-energy alpha-particles. The aim of this study was to investigate in vivo effects of the high linear energy transfer (LET) emitter (211)At on tumor growth and outcome in nude mice.
We administered radioastatide in a fractionated therapy scheme to NMRI nude mice harboring rapidly growing solid tumors established from a papillary thyroid carcinoma cell line genetically modified to express NIS (K1-NIS). Animals were observed over 1 year. Tumor growth, body weight, blood counts, survival, and side effects were measured compared with control groups without therapy and/or lack of NIS expression.
Within 3 months, radioastatide caused complete primary tumor eradication in all cases of K1-NIS tumor-bearing nude mice (n = 25) with no tumor recurrence during 1 year follow-up. Survival rates of the K1-NIS/(211)At group were 96% after 6 months and 60% after 1 year, in contrast to those of control groups (maximum survival 40 days).
Our study indicates that (211)At represents a promising substrate for NIS-mediated therapy of various cancers either with endogenous or gene transfer-mediated NIS expression.
目前正在多项试验中探索钠/碘同向转运体（NIS）基因，以利用其β辐射通过放射性碘（（131）I）根除实验性癌症。我们最近对另一种卤化物——放射性砹（（211）At）的NIS特异性细胞摄取进行了表征，（211）At会发射高能α粒子。本研究的目的是调查高传能线密度（LET）发射体（211）At对裸鼠肿瘤生长和结局的体内影响。
我们采用分次治疗方案，向携带由经过基因改造以表达NIS的甲状腺乳头状癌细胞系建立的快速生长实体瘤的NMRI裸鼠给药放射性砹。对动物进行了1年的观察。测量肿瘤生长、体重、血细胞计数、存活率和副作用，并与未接受治疗和/或缺乏NIS表达的对照组进行比较。
在3个月内，放射性砹使所有携带K1-NIS肿瘤的裸鼠（n = 25）的原发性肿瘤完全根除，在1年的随访期间无肿瘤复发。K1-NIS/（211）At组6个月后的存活率为96%，1年后为60%，而对照组的存活率（最大存活40天）则不同。
我们的研究表明，无论是内源性还是基因转移介导的NIS表达，（211）At都是NIS介导的各种癌症治疗的有前景的底物。
